The morphogenesis of a total of 40 salivary gland adenomas (pleomorphic adenomas (30), basal cell adenomas (5), and myoepitheliomas (5)), and its association with hepatocyte growth factor (HGF), hepatocyte growth factor receptor c-Met, and Bcl-2, was investigated. The presence of these proteins, and their mRNA expression, were determined by immunohistochemistry and RT-PCR analysis. Localization of HGF mRNA in the pleomorphic adenomas was also examined, using in situ hybridization with digoxygenin-labeled oligonucleotide probes. Apoptosis was detected in histological sections by a modified 3'-end DNA labeling method.
1) Immunoreactivity for HGF was localized consistently on the luminal cells, which were normal or neoplastic ductal cells. Immunoreactivity was absent on other components. Localization of HGF mRNA was also observed on luminal cells of the pleomorphic adenomas. In addition, RT-PCR analysis also showed an HGF-positive signal. These results suggest that HGF may play an important role in morphogenesis of the duct in salivary gland adenomas.
2) Expressions of Bcl-2 protein were mainly localized in the neoplastic myoepithelium of the pleomorphic and basal cell adenomas, but were not seen in either normal salivary gland or myoepitheliomas. Immunoreactivity was greater in pleomorphic adenomas than in basal cell adenomas. The mRNA signals for Bcl-2 were detected by RT-PCR analysis in the pleomorphic adenomas. Compared with HGF expression, the histological localization of Bcl-2 was different. The frequency of apoptosis was higher in basal cell adenomas than in pleomorphic adenomas, whereas no apoptosis was detected in myoepitheliomas. These results suggest that an association between Bcl-2 expression and apoptosis may play an important role in the appearance of histological variations in salivary gland adenomas.
3) Expression of c-Met protein was seen in the neoplastic myoepithelium of pleomorphic adenomas and basal cell adenomas. In the pleomorphic adenomas, c-Met expression cases were almost consistent with Bcl-2 expression cases. These results suggest possibility that there is a relation between c-Met and Bcl-2.
In conclusion, it is suggested that HGF, c-Met and Bcl-2 may play an important role in the morphogenesis of salivary gland adenoma.
